Inhibition of 11B-hydroxysteroid dehydrogenase type 1 as a promising therapeutic target

Malgorzata Wamil, Jonathan R. Seckl*

*Corresponding author for this work

Research output: Contribution to journalLiterature reviewpeer-review

Abstract / Description of output

Chronically elevated glucocorticoid levels cause obesity, diabetes, heart disease, mood disorders and memory impairments. 11 beta-hydroxysteroid dehydrogenase type 1 (11 beta-HSD1) catalyses intracellular regeneration of active glucocorticoids (cortisol, corticosterone) from inert 11 -keto forms in liver, adipose and brain, amplifying local action. Obese humans and rodents show increased I I beta-HSD I in adipose tissue. Transgenic mice overexpressing 11 beta-HSDI selectively in adipose tissue faithfully recapitulate metabolic syndrome. Conversely, 11 beta-HSD I knockout mice have a 'cardioprotective' phenotype, whose effects are also seen with I 1 beta-HSD1 inhibitors in rodents. However, any major metabolic effects of 11 beta-HSD1 inhibition in humans are, as yet, unreported. 1 1 beta-HSD 1 null mice also resist congitive decline with ageing, and this is seen in humans with a prototypic inhibitor. Thus 11 beta-HSD1 inhibition is an emerging pleiotropic therapeutic target.

Original languageEnglish
Pages (from-to)504-520
Number of pages17
JournalDrug Discovery Today
Volume12
Issue number13-14
Publication statusPublished - Jul 2007

Keywords / Materials (for Non-textual outputs)

  • CORTISONE REDUCTASE DEFICIENCY
  • HEPATIC INSULIN SENSITIVITY
  • OBESE ZUCKER RATS
  • ENCODING 11-BETA-HYDROXYSTEROID DEHYDROGENASE
  • POLYCYSTIC-OVARY-SYNDROME
  • PITUITARY-ADRENAL AXIS
  • HUMAN ADIPOSE-TISSUE
  • HEXOSE-6-PHOSPHATE DEHYDROGENASE
  • IN-VIVO
  • ENDOPLASMIC-RETICULUM

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